We previously reported South African children living with HIV (HIV+) randomized to remain on a lopinavir/ritonavir (LPV/r)-based antiretroviral therapy (ART) regimen had lower bone mass compared to HIV+ children randomized to switch to efavirenz (EFV) and to controls without HIV (HIV-). This analysis presents two additional years of follow-up.
The CHANGES Bone Study tracks bone health in HIV+ and HIV- children at one site in Johannesburg, South Africa. A single technician blinded to HIV status and treatments analyzed total body (TB) bone mineral content (BMC) by dual-energy X-ray absorptiometry (DXA) at baseline, 12 and 24 months (mean 2.1, 3.1 and 4.1 years after ART switch, respectively). TB BMC Z-scores adjusted for sex, race, age, and height were generated using reference norms from the US Bone Mineral Density in Childhood Study. During follow-up three groups were compared: HIV+ children on LPV/r or EFV and HIV- children.
207 (94.1%) HIV+ children and 200 (90.9%) HIV- controls completed three visits. Mean ages at the third visit were 8.4 (SD=1.3) and 9.0 (SD=1.6) years respectively. Over 2 years of follow-up, TB BMC Z-scores declined for all three groups: HIV+ on EFV, HIV+ on LPV/r, and HIV- controls at a rate of -0.12, -0.13 and -0.11 per year, respectively. TB BMC Z-scores at baseline, 12 and 24 months were significantly higher among HIV+ on EFV compared to HIV+ on LPV/r (Figure 1A: -0.77 vs -1.14, p=0.04; -0.94 vs -1.34, p<0.01; -1.01 vs -1.40, p=0.04, respectively). With the exception of boys at baseline, differences in BMC Z-scores between ART groups were significant in girls and boys at all three visits (Figure 1B). TB BMC Z-scores at baseline, 12 and 24 months among HIV+ children on EFV were not significantly different from HIV- controls (-0.77 vs -0.82, p=0.54; -0.94 vs -0.95, p=0.95; -1.01 vs -1.04, p=0.71, respectively). Changes of TB BMC Z-scores from baseline to 24 months were not significantly different between children on EFV and those on LPV/r (-0.21 vs -0.26, p=0.53).
Despite a slight overall decline in bone mass among HIV+ compared with US population norms over 2 years, bone mass remained higher in HIV+ children switched to EFV compared to those continuing LPV/r, even 4 years after switching. Further, HIV+ children switched to EFV had similar BMC Z-scores as HIV- controls. These findings support our previous recommendations to switch children with sustained viral suppression on first line regimen with LPV/r to EFV.